The main objective of this proposal is to devise a treatment of systemic lupus in mice using the principle of of carrier determined tolerance to nucleic acid anitgens in combination with immunosuppressive drugs. The long-term goal is to provide a data base that will be applicable to the treatment of the disease in human beings. In addition, tolerance to nucleic acid antigens will be used to seek new information in three different areas of investigation: a) the cellular mechanism of tolerance to nucleic acids: b) the genetic basis of tolerance; and c) the relationship, if any, of suppression of antibodies to DNA to the expression of viral antigens and anti-viral antibodies.